The proposed research involves the study and development of a variety of carbon-carbon bond forming reactions which are particularly well suited for use in the synthesis of natural products possessing desirable antibiotic or antitumor activity, and the application of these methods to total syntheses of such compounds. Specific examples include antibiotics such as colletodiol, calcimycin, carbomycin and tylosin, as well as the antitumor agent herbimycin. A synthetic investigation of the very promising rhizoxin family of antitumor agents, designed not only to culminate in a successful laboratory synthesis but also to reveal structural features required for activity and to provide simpler biologically active analogues, is also proposed as an example of how such methodology allows for particularly concise syntheses of biologically important compounds.